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Antiviral Therapy in Hepatitis B Virus (HBV)-Related Advanced Liver Disease Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00823550
Recruitment Status : Unknown
Verified January 2009 by Yonsei University.
Recruitment status was:  Active, not recruiting
First Posted : January 15, 2009
Last Update Posted : December 16, 2010
Information provided by:

Study Description
Brief Summary:
This is a randomized, open label, phase IV, multicenter study for efficacy and safety of lamivudine versus entecarvir therapy in HBV-related advanced liver disease patients with high viral load and normal or slightly elevated transaminase.

Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Drug: Entecavir Drug: Lamivudine Phase 4

Detailed Description:
Currently, treatment guidelines for the management of chronic hepatitis B (CHB) recommend that patients with serum HBV DNA > 105 copies/ml and elevated ALT levels greater than two times the upper limit of normal (ULN) are obvious candidates for antiviral therapy. Guidelines also suggest that antiviral therapy be considered in CHB patients with high viral load, if a biopsy shows significant liver disease despite ALT ≤ 2× ULN. Data from recent trials in hepatitis B patients who present with normal to minimally elevated ALT (≤ 2× ULN) indicate that significant hepatic pathology could still be found. Serum ALT level may not accurately predict activity of liver damage. ALT is a poor predictor of outcome and therefore is not a suitable criterion for antiviral therapy in chronic hepatitis B infection. Also, a recent large randomized controlled clinical trial comparing lamivudine maintenance and placebo in advanced fibrosis (Ishak fibrosis score ≥ 4) suggests that sustained viral suppression with antiviral therapy is linked to reduced risk for disease progression. (Liaw YF et al. NEJM 2004;351:1521-1531)

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 462 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open Label, Phase IV, Multicenter Study for Efficacy and Safety of Lamivudine Versus Entecarvir Therapy in HBV-related Advanced Liver Disease Patients With High Viral Load and Normal or Slightly Elevated Transaminase
Study Start Date : January 2009
Estimated Primary Completion Date : July 2014
Estimated Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: A
entecavir 0.5 mg QD
Drug: Entecavir
entecavir 0.5 mg QD
Other Name: Baraclude 0.5mg
Active Comparator: B
lamivudine 100 mg QD
Drug: Lamivudine
lamivudine 100 mg QD
Other Name: Zeffix 100mg

Outcome Measures

Primary Outcome Measures :
  1. Time to disease progression as defined by the first occurrence of any of the cirrhosis compolications [ Time Frame: 5 years ]

Secondary Outcome Measures :
  1. Proportion of patients achieving either HBV DNA level ≤ 60 IU/mL Proportion of patients with ALT normalization Proportion of patients with HBeAg loss and seronconversion Proportion of patients with virologic breakthrough [ Time Frame: at months 12, 24, 36, 48, and 60 ]

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria

  • Male and female, 18 years of age or older
  • HBsAg positive for more than 6 months
  • Serum HBV DNA > 2,000 IU/ml
  • Serum ALT < 2 X ULN on two consecutive occasions at least 3 months apart
  • Naïve to nucleoside or nucleotide therapy
  • On liver biopsy, fibrosis score ≥ 3 according to METAVIR scoring system (within 2 years of Day 0)
  • If liver biopsy is not available, subjects must have two of the following items

    • Overt findings of cirrhosis by radiologic evidence (MRI, CT, US)
    • Gastrointestinal varices
    • Platelet count < 100,000,Splenomegaly (Spleen size - 12cm)
  • The patient who is willing and able to provide written informed consent to participate in this study

Exclusion criteria

  • A history of SBP, variceal bleeding, HEP, HCC
  • Decompensated liver disease (Child-Pugh score > 10)
  • Co-infected with HCV or HIV
  • History of any other forms of liver disease.
  • Patient who is pregnant or breastfeeding
  • Treatment with immunosuppressive, immunomodulatory agents or antiviral agents within 6 months prior to study entry
  • A history of liver transplantation or planned for liver transplantation
  • A history of any other medical disease or condition that would make the patients unsuitable for the study.
  • Patient is currently abusing alcohol or illicit drugs or has a history of alcohol abuse or illicit substance abuse within the preceding 2 years.
  • Patient is enrolled or plans to enroll in another clinical trial of an investigational agent while participating in this study.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00823550

Korea, Republic of
Severance Hospital
Seoul, Korea, Republic of
Sponsors and Collaborators
Yonsei University
Severance Hospital
Kangbuk Samsung Hospital
Konkuk University Hospital
Chung-Ang University
Ajou University
Inha University Hospital
Soonchunhyang University Hospital
The Catholic University of Korea
Hallym University Medical Center
Kyungpook National University
Keimyung University
Korea University Anam Hospital
Korea University
Hanyang University
Inje University
Pusan National University Hospital
Bristol-Myers Squibb
Study Chair: Kwnag-Hyub Han, MD Yonsei Univsersity College of Medicine
Study Director: Jun Yong Park, MD Yonsei Univsersity College of Medicine
More Information

Responsible Party: Kwang-Hyub Han, Department of Internal Medicine, Yonsei University College of Medicine
ClinicalTrials.gov Identifier: NCT00823550     History of Changes
Other Study ID Numbers: 4-2008-0296
First Posted: January 15, 2009    Key Record Dates
Last Update Posted: December 16, 2010
Last Verified: January 2009

Keywords provided by Yonsei University:
Chronic hepatitis B
Advanced fibrosis

Additional relevant MeSH terms:
Hepatitis A
Hepatitis B
Liver Diseases
Hepatitis B, Chronic
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents